Drug information of Desvenlafaxine

Desvenlafaxine

Drug group:

Desvenlafaxine (O-desmethylvenlafaxine) the major active metabolite of venlafaxine, is an antidepressant from the serotonin norepinephrine reuptake inhibitor (SNRI) class. Desvenlafaxine may be used to treat major depressive disorder.

Mechanism of effect

Desvenlafaxine inhibits neurotransmitter reuptake in serotonin, norepinephrine, and dopamine transporters. Desvenlafaxine inhibits serotonin transporters with 10 times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity.

Pharmacodynamic

Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptors in vitro. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity again the cardiac potassium channel, hERG, in vitro. Compared to other SNRIs, desvenlafaxine undergoes simple metabolism, has a low risk of drug-drug interactions and does not have to be extensively titrated to reach a therapeutic dose.

Pharmacokinetics

Bioavailability: 80%

Peak plasma time: 7.5 hr

Ingestion of a high-fat meal (800-1000 calories) increased desvenlafaxine peak plasma concentration about 16% and had no effect on AUC

Protein bound: 30%

Vd: 3.4 L/kg

Metabolism

Primary: Conjugation (UDP-glucuronosyltransferase isoform mediated)

Minor: CYP3A4 oxidative metabolism (N-demethylation)

Enzymes inhibited: CYP2D6 (minimally)

Half-life: 11 hr (prolonged in renal or hepatic dysfunction)

Dialyzable: No

Excretion, unchanged drug: Urine (45%)

Excretion, metabolite: 19% (glucuronide); <5% (oxidative metabolite [N,O-didesmethylvenlafaxine])

Dosage

Adult

Major Depressive Disorder

50 mg PO once daily

Higher dosages, up to 400 mg/day, have been used but have not been proved more efficacious; increased side effects have been reported

 

Pediatric

Safety and efficacy not established

Alerts

Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Use caution in patients with history of seizure disorders

Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants

May precipitate shift to mania or hypomania in patients with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen for bipolar disorder patients presenting with depressive symptoms

Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders

Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased

Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion

Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort

May impair congnitive abilities; use caution operating heavy machinery

Taper dose when possible and monitor for discontinuation symptoms; adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures

Serotonin syndrome

  • Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort
  • Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors
  • Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
  • Monitor for the emergence of serotonin syndrome
  • Discontinue treatment with desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment
  • If concomitant use of desvenlafaxine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms

Drug interactions overview

  • Concomitant use of desvenlafaxine increases peak plasma concentration and AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drugs
  • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk
  • False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine

Black Box Warnings

Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies

Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years

In children and young adults, initiate only if benefits greatly outweigh risks

Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments

Patient’s family should communicate any abrupt behavioral changes to healthcare provider

Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

Not approved for use in pediatric patients

Points of recommendation

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Take desvenlafaxine with water at the same time each day, with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

Your blood pressure will need to be checked often.

It may take several weeks before your symptoms improve. Do not stop using desvenlafaxine without first talking to your doctor. You may have unpleasant side effects if you stop taking this medicine suddenly.

Some tablet forms of desvenlafaxine are made with a shell that is not absorbed or melted in the body. Part of the tablet shell may appear in your stool. This is a normal side effect and will not make the medicine less effective.

Store at room temperature away from moisture and heat.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Pregnancy level

Group c - Not adequate studies in pregnant women

Related drugs

Duloxetine , Venlafaxine , Milnacipran


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